Drugs such as praziquantel are available for the treatment of uncomplicated schistosomiasis. They provide interim control of the disease. However the challenge today is not so much in the clinical management of individual patients but rather in the control of transmission and reduction of morbidity in endemic populations. A long term approach to schistosomiasis control is a vaccination program that would result in reduced transmission and reduced morbidity. The major goal of this research is to evaluate the vaccine potential of specific schistosome molecules. To accomplish part of this goal the investigator employs a model of immunity that uses attenuated parasites to induce up to 90 percent protection against challenge infection. Immunity in this vaccine model primarily involves T cells that recognize antigens associated with the target of the immune response, the schistosomula and, as a result of this recognition mediate a schistosomicidal response. Schistosomula antigens that stimulate T cells to mediate a cidal response will be identified and the genes that encode them isolated. By isolating the DNA encoding a schistosome antigen, the PI plans to sequence the gene, deduce the amino acid sequence of the antigen, clone the cDNA into a eucaryotic expression vector and deliver it to animals as a naked DNA vaccine to test its efficacy in conferring protective immunity. A second strategy will test the hypothesis that antioxidants play an important role in immune evasion by adult parasites. To test the hypothesis and thus determine if adult worms can be a target for immune elimination, various antioxidants (superoxide dismutase, glutathione peroxidase and gluthathione-s-transferase) will be used singly and in combination in protection experiments. Should adult worms turn out to be a viable vaccine target, then a significant advance in schistosome vaccine development will have been achieved. In any case those schistosome antigens that demonstrate significant protective immunity will be characterized further by defining T and B cell epitopes for inclusion in a subunit vaccine. The ultimate goal of the research is to develop an efficacious vaccine that contains parasite specific epitopes.
| Corstjens, Paul L A M; De Dood, Claudia J; Kornelis, Dieuwke et al. (2014) Tools for diagnosis, monitoring and screening of Schistosoma infections utilizing lateral-flow based assays and upconverting phosphor labels. Parasitology 141:1841-55 |
